The general area of pulmonary host defenses and nosocomial infections is being investigated, using Pseudomonas pneumonia as the prototype infection because of its frequent occurrence in immunosuppressed patients who are most susceptible to opportunistic micro-organisms. Initial work has been done in rabbits to explore ways of manipulating antibody production in the respiratory tract and to assess the effectiveness of these antibodies in promoting phagocytosis and killing by alveolar macrophages. IgG was found to be the principal opsonin in the lung; maximal amounts of IgG opsonic antibody could be produced with a combination of intramuscular and intranasal (local secretory IgG produced) immunization. IgA antibody was induced with intranasal vaccination but was judged to have less opsonic activity. Competent phagocytic cells are essential for the pulmonary defenses. In addition, intranasal immunization with Pseudomonas lipopolysaccharide sensitized respiratory lymphocytes which could be induced to release migration inhibition factor, which is an in vitro correlate of delayed hypersensitivity or cellular immunity. However, evidence of cellular immunity in the respiratory tract was transient following primary immunization and persisted only about 3 weeks. Thus, the importance of cellular immunity in the coordinated host defense of the lung against Pseudomonas infection needs to be assessed further. Where possible, similar studies have been conducted in human subjects. A Pseudomonas vaccine (Parke-Davis Inc., IND 185 BOB) has been evaluated in patients considered at high risk to develop Pseudomonas infections such as those with acute hematologic malignancies, cystic fibrosis, and chronic pulmonary diseases. The immunogenicity of the vaccine is good but the protective effects (i.e., humoral agglutinating antibodies against somatic Pseudomonas antigens) were not striking in the small number of subjects available for comparison (about 50).